PMID- 30417207 OWN - NLM STAT- MEDLINE DCOM- 20190701 LR - 20210826 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 46 IP - 1 DP - 2019 Feb TI - Leptin is a direct transcriptional target of EGR1 in human breast cancer cells. PG - 317-324 LID - 10.1007/s11033-018-4474-3 [doi] AB - Leptin is a cytokine that regulates energy metabolism. Leptin can promote breast cancer progression in obese women. However, the mechanism of regulation of leptin expression in breast cancer cells is unclear. Tumor necrosis factor-alpha (TNF-alpha) stimulated the transcription of the leptin gene. Using mutant promoter constructs, we demonstrated that the EGR1-binding motif in the proximal region of the leptin gene is required for leptin transcription by TNF-alpha. Forced expression of EGR1 stimulated leptin promoter activity, whereas silencing of EGR1 by RNA interference reduced TNF-alpha-induced leptin protein accumulation. The ERK1/2 pathway contributed to the expression of EGR1 and leptin by TNF-alpha. Our results suggest that EGR1 targets the leptin gene in response to TNF-alpha stimulation in breast cancer cells. FAU - Kim, JuHwan AU - Kim J AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Jung, Euitaek AU - Jung E AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Choi, Jihye AU - Choi J AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Min, Dong Yeong AU - Min DY AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Lee, Young Han AU - Lee YH AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. AD - Cancer and Metabolism Institute, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Shin, Soon Young AU - Shin SY AUID- ORCID: 0000-0002-1075-0011 AD - Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. shinsy@konkuk.ac.kr. AD - Cancer and Metabolism Institute, Konkuk University, Seoul, 05029, Republic of Korea. shinsy@konkuk.ac.kr. LA - eng GR - 2016R1A2B4008570/National Research Foundation of Korea/ PT - Journal Article DEP - 20181111 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (DNA-Binding Proteins) RN - 0 (EGR1 protein, human) RN - 0 (Early Growth Response Protein 1) RN - 0 (Leptin) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Binding Sites MH - Breast Neoplasms/genetics/*metabolism MH - Cell Line, Tumor MH - DNA-Binding Proteins/genetics MH - Early Growth Response Protein 1/genetics/*physiology MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - Leptin/genetics/*physiology MH - MAP Kinase Signaling System/genetics/physiology MH - Promoter Regions, Genetic/drug effects/genetics MH - RNA, Messenger/metabolism MH - Transcription Factors/genetics MH - Transcription, Genetic/drug effects MH - Transcriptional Activation/drug effects MH - Tumor Necrosis Factor-alpha/genetics/physiology OTO - NOTNLM OT - Breast cancer OT - EGR1 OT - ERK1/2 OT - Leptin OT - Tissue necrosis factor alpha EDAT- 2018/11/13 06:00 MHDA- 2019/07/02 06:00 CRDT- 2018/11/13 06:00 PHST- 2018/09/04 00:00 [received] PHST- 2018/11/07 00:00 [accepted] PHST- 2018/11/13 06:00 [pubmed] PHST- 2019/07/02 06:00 [medline] PHST- 2018/11/13 06:00 [entrez] AID - 10.1007/s11033-018-4474-3 [pii] AID - 10.1007/s11033-018-4474-3 [doi] PST - ppublish SO - Mol Biol Rep. 2019 Feb;46(1):317-324. doi: 10.1007/s11033-018-4474-3. Epub 2018 Nov 11.